Engineered nano-particles are defined as particles with diameter of less than 100 nm. A nano-aerosol is defined as a gas flow containing nano-particles. Workers that manufacture nano-particles, either deliberately or as a result of other industrial processes, are at risk from exposure to nano-particles via inhalation. Research studying the exposure of humans or animals to nano-particles by performing inhalation toxicity studies requires specially designed methods for the stable generation and delivery of nano-particles as nano-aerosols that simultaneously maintains high nano-particle concentration in the air, and which avoids coagulation and agglomeration of the nano-particles. Additionally, it may be beneficial to introduce certain materials as nano-particles as nano-aerosols to either animals or humans to treat disease or other harmful conditions. To date, no methods or apparatus have been shown to satisfactorily accomplish these objectives for wide range of compounds.
In a recently published paper (Schmoll, L. H. (2009). Nanotoxicology, 3(4): 265-275.) several known technologies were investigated to generate nano-aerosol out of commercially available nano-powder. The authors concluded that “none of the generation methods except for electrospray were able to produce an aerosol with a size distribution similar to that of the primary particle size indicated by the manufacturer, but most were capable of producing an agglomerate size distribution with a geometric mean <200 nm.” The authors also noted that “electrospray was not able to produce a consistent concentration over time for all particles tested” (because of well known capillary clogging issues inherent for electrospray technology).
In the paper A R Martin, R B Thompson and W H Finlay, “MRI Measurement of Regional Lung Deposition in Mice Exposed Nose-Only to Nebulized Superparamagnetic Iron Oxide Nanoparticles” JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Volume 21, Number 4, 2008, pp. 335-341, Finlay et al. describe the use of superparamagnetic iron oxide nanoparticles in magnetic targeting of inhaled aerosols to localized sites within the lung and as contrast agents in magnetic resonance imaging (MRI). In the experiments described in the paper, Finlay et al. examine the feasibility of measuring regional lung deposition of iron oxide nanoparticles using MRI. Mice were exposed nose-only to nebulized superparamagnetic iron oxide nanoparticles. The droplet size distribution in the inhalation chamber was measured using a time-of-flight device. Regional concentrations of iron in the left and right lung were assessed with MRI by measuring the longitudinal relaxation times (T1) of the lung tissue in exposed mice, compared to a baseline group. The total mass of iron that deposited in the lung of each exposed mouse was only 0.0006+/−0.0002% (mean+/−1 standard deviation, n+/−6) of the mass of iron introduced into the inhalation chamber. Based on these results, estimation shows that the delivery-deposition efficiency, measured as the [Total Deposited Mass]/[Total Inhaled Mass] of only 0.039%. Finlay et al. state that “This result is consistent with previous studies, in which nose-only, flow-by inhalation chambers have been shown to be extremely inefficient in terms of the amount of aerosol delivered to the lungs of rodents.” citing Nadithe V, Rahamatalla M, Finlay W H, Mercer J R, and Samuel J: Evaluation of nose-only aerosol inhalation chamber and comparison of experimental results with mathematical simulation of aerosol deposition in mouse lungs. J Pharm Sci. 2003; 92:1066-1076 and Costa D L, Lehmann J R, Winsett D, Richards J, Ledbetter A D, and Dreher K L: Comparative pulmonary toxicological assessment of oil combustion particles following inhalation or instillation exposure. Toxicol Sci. 2006; 91:237-246. The inefficiency of introducing materials as an aerosol of few micron size into animals via nasal inhallation as described by Finlay and others is problematic because in many cases the materials that are to be tested or used via nasal inhalation are expensive and hard to manufacture.
Accordingly, there remains a need for methods and apparatus that provide stable generation and delivery of nano-particles of wide range of compounds in aerosols that simultaneously maintain high nano-particle concentration in the air, and which avoid coagulation and agglomeration of the nano-particles. There is a further need for methods and apparatus that provide stable generation and delivery of nano-particles of wide range of compounds in aerosols in a manner that improves the efficiency of introducing these nano-particles into animals through nasal inhalation of the nano-particles.